@Article{ecn.2026.078477,
AUTHOR = {Kavee Shree Sukumaran, Nelli Giribabu, Naguib Salleh},
TITLE = {Cytokine signalling in vaginal epithelial cells: mechanistic insights into epithelial immunity and inflammatory milieu in vulvovaginal candidiasis},
JOURNAL = {European Cytokine Network},
VOLUME = {37},
YEAR = {2026},
NUMBER = {2},
PAGES = {79--95},
URL = {http://www.techscience.com/ECN/v37n2/67940},
ISSN = {1952-4005},
ABSTRACT = {Vulvovaginal candidiasis (VVC) is one of the most prevalent mucosal infections worldwide, experienced by women throughout their reproductive years. <i>Candida albicans</i> is involved in 85–95% of all VVC cases and given the stronger correlation between the severity of epithelial cytokine responses, rather than fungal burden, with VVC symptoms, this disease is fundamentally immunopathological. VVC is believed to be initiated by a cascade of events that leads to vaginal epithelial cell (VEC) damage. These cells act as immune sentinels and can detect fungal morphotypes as well as virulence factors through diverse pattern recognition receptors, such as TLRs, C-type lectin receptors, and nucleotide-binding oligomerization domain-like receptors. Recognition of <i>C. albicans</i> can trigger complex intracellular signalling cascades in VECs that involve NF-κB, MAPK, and activator protein-1, which culminate in robust production of proinflammatory cytokines, chemokines, and alarmins. The hypha-specific peptide toxin, candidalysin can also initiate VEC membrane damage, which leads to nucleotide-binding oligomerization domain, leucine-rich repeat family and pyrin domain-containing protein 3 inflammasome assembly in the VECs. The resulting inflammatory events lead to robust recruitment of neutrophils, which, although they fail to effectively clear the fungus, add to even more tissue damage, contributing to the severity of VVC symptoms. This review synthesises the molecular- and cellular-based evidence to clarify the role of VEC-related immune activation in the development of VVC and to provide a new understanding that VVC signs and symptoms are predominantly immune-related.},
DOI = {10.32604/ecn.2026.078477}
}